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Summary: The use of black soldier fly larvae (BSFL) to valorise different organic waste streams and the subsequent use of resulting larvae as a feedstock ingredient is increasing rapidly in several regions across the globe. The lack of knowledge about several safety issues including chemical contaminants (e.g. heavy metals) seems to affect the upscaling and commercialisation of this product. This study evaluates the safety of the BSFL against chemical contaminants including heavy metals and mycotoxins in both BSFL and frass samples reared with different food waste streams (e.g. soy waste, customised bread‐vegetable diet, food waste mixture, supermarket and childcare centre) from two commercial production facilities. The effect of larval instars and post‐harvest treatments (e.g. blanching and drying) on the safety of the BSFL was also investigated. The concentration of heavy metals was primarily influenced by the concentration in the food waste streams. The concentration was also higher in 6th instar compared to 5th instar larvae. The effect of blanching and drying have a varied effect on the concentration of heavy metals. Mycotoxins were found to be below the limit of quantification for all samples. The outcomes of this study indicated that BSFL grown on food waste streams and the resulting frass is safe against different heavy metals analysed. The findings of this study will assist the commercial BSFL manufacturers with the identification of relevant control points to ensure the chemical safety of their products. Therefore, encourage the use of different food waste streams as feedstock for rearing BSFL. [ABSTRACT FROM AUTHOR]

Background: Attrition continues to be a major hurdle for addiction treatment. Through the prism of the attachment theory, this phenomenon can be understood as a manifestation of the patient's insecure attachment style, needing a highly-responsive care delivery. We developed an electronic health mobile application, co-designed with patients, aimed at helping healthcare teams respond to their patients' needs, and fostering adherence to care. This acceptability study evaluated patients everyday use of the application for eight weeks, assessing their satisfaction with the system, and its integration within professionals' current practice in our center. Methods: This single-center, prospective study was conducted between January 2022 and December 2022. 24 adult patients with any type of addiction were included. They were granted access to the application for eight weeks, and were invited to complete the System Usability Scale questionnaire regarding their satisfaction with application's usability at the end of the study. The application uses active self-reports, which are later discussed with the healthcare team, and foster both the working alliance and the decision-making process. Results: 17 patients out of 24 reached the primary endpoint. On average, over the eight-weeks period, patients logged in the application 38.2 times, and sent 5.9 messages to the healthcare team. Interestingly, 64.3% of the user logins were recorded outside of our center's working hours (either from 5 p.m. to 9 a.m., or during week-ends and bank holidays), and 70.8% of the patients logged into the application at least one time between 10 p.m. and 8 a.m. 18 patients completed the System Usability Scale questionnaire, which averaged a score of 81.8 out of 100. Healthcare professionals logged in the application's messaging system 4.5 times a day on average. Conclusions: This preliminary study shows promising results, as patients engaged well with various components of the application. It was moreover possible for healthcare workers in our center to integrate this tool in their daily activities. More work is needed to better understand the various patients' needs regarding the application, further strengthen their adherence to the intervention, and understand professionals' motivations to use the application. Trial registration: ClinicalTrials.gov, Identifier: NCT04659954. Registered 09 December 2020, https://clinicaltrials.gov/study/NCT04659954. [ABSTRACT FROM AUTHOR]

Background: In Australia, one-third of people ≥15 years perform regular resistance training and 90% of those do not meet current health guidelines. All age groups should engage in regular resistance exercise, to maintain strength and function. Objectives: To identify trends in powerlifting competition participation in Australia by sex and age group from 1968 to 2022, and to compare the strength of powerlifting competitors to population age- and sex-based normative values. Method: The number of unique participants and total competition entries for each year were analysed using Australian powerlifting competition data. Subdomains of age and sex were investigated, and mean ± SD, frequency, range, and trend analyses reported. United Nations age classifications were used to identify age trends. Comparisons to population strength norms were explored descriptively. Results: We included 21,514 individual competitors from 1942 powerlifting competitions between 1968 and 2022. Exponential growth was seen in competition entries from 115 in 1981, to 759 in 1994, 1014 in 2011, and to 6803 in 2022, (R2 = 0.86). At first participation 18–25-year olds (51.1%) followed by ≥36 years (16%) were most represented. Strength comparison to available population norms demonstrates superior upper- (bench press [most competitors above 70th percentile) and lower-body (squat [majority rated 'excellent') strength. Conclusions: Superior strength levels of powerlifters further the evidence base for this sport as an effective way to develop muscular strength, with low injury. We advocate for public health promotion and additional support for powerlifting as an underutilised community health tool. [ABSTRACT FROM AUTHOR]

This article reviews recent literature on sanctions from international law, political science, sociology, anthropology, and history. It shows how the literature during the comprehensive sanctions decade (the 1990s), with a largely critical view on sanctions in the age of globalization, was co-opted by the targetization of sanctions in the sanctions miniaturization decade (the 2000s). It then reviews the sanctions literature in sociology and anthropology during the sanctions enforcement decade (the 2010s), addressing the transnational characteristics of sanctions, their infrastructural materiality in the digital economy, and the deputization of private actors to police their implementation. Last, the article reviews the literature in colonial governmentality to encourage sanctions specialists to take a longer-term view of transnational orders of sanctions. This section ends with a call to decolonize sanctions research—or rather, to question the colonial origins of sanctions as an instrument of world making so that a properly decolonial perspective on sanctions can be elaborated. [ABSTRACT FROM AUTHOR]

Simple Summary: Newborn calves rely on consuming the first milk, colostrum, to transfer important proteins and cells for protection from pathogens. Lymphocytes compose a fraction of the cells transferred through the colostrum to the calf, known as T and B cells. In cattle, a subset of B cells possess a unique receptor with an ultralong protein insert, known as ultralong complementarity determining region 3 (CDR3), which may be crucial in neutralizing viruses. This study found that colostrum had a significantly higher percentage of B cells with ultralong CDR3s than B cells from the blood. This finding may indicate an important role and selective transfer of B cells in colostrum with an ultralong CDR3. In cattle, colostral maternal immunoglobulins and lymphocytes transfer across the neonate's intestinal epithelium to provide protection against pathogens. This study aimed to compare repertoires of B cell populations in blood and colostrum in cows for the first time, with an emphasis on ultralong complementarity determining region 3 (CDR3, ≥40 amino acids). Blood mononuclear cells (BMCs, n= 7) and colostral cells (n = 7) were isolated from Holstein-Friesian dairy cows. Magnetic-activated cell sorting was used to capture IgM and IgG B cells from BMCs. Colostral cells were harvested by centrifugation. RNA was extracted and cDNA was produced; IgM and IgG transcripts were amplified using polymerase chain reactions. Amplicons were sequenced using the Nanopore Native barcoding kit 24 V14 and MinION with R10.4 flow cells. In colostrum, there was a significantly greater percentage of IgM B cells with ultralong CDR3s (8.09% ± 1.73 standard error of the mean) compared to blood (4.22% ± 0.70, p = 0.05). There was a significantly greater percentage of IgG B cells in colostrum with ultralong CDR3s (12.98% ± 1.98) compared to blood (6.61% ± 1.11, p = 0.05). A higher percentage of IgM and IgG B cells with ultralong CDR3s in colostrum may be indicative of a potential role in protecting the neonate. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential nutrient that has gained attention for its impact on the human immune system. The purpose of this review is to explore Se's immunomodulatory properties and to make up-to-date information available so novel therapeutic applications may emerge. People acquire Se through dietary ingestion, supplementation, or nanoparticle applications. These forms of Se can beneficially modulate the immune system by enhancing antioxidant activity, optimizing the innate immune response, improving the adaptive immune response, and promoting healthy gut microbiota. Because of these many actions, Se supplementation can help prevent and treat pathogenic diseases, autoimmune diseases, and cancers. This review will discuss Se as a key micronutrient with versatile applications that supports disease management due to its beneficial immunomodulatory effects. Further research is warranted to determine safe dosing guidelines to avoid toxicity and refine the application of Se in medical treatments. [ABSTRACT FROM AUTHOR]

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Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research in growing datasets. Here, the authors screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes, showing overall concordance between female and male individuals. [ABSTRACT FROM AUTHOR]

Infection during the perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) transforms brain lipid composition in the offspring and protects the neonatal brain from stroke, in part by blunting injurious immune responses. Critical to the interface between the brain and systemic circulation is the vasculature, endothelial cells in particular, that support brain homeostasis and provide a barrier to systemic infection. Here, we examined whether maternal PUFA-enriched diets exert reprograming of endothelial cell signalling in postnatal day 9 mice after modeling aspects of infection using LPS. Transcriptome analysis was performed on microvessels isolated from brains of pups from dams maintained on 3 different maternal diets from gestation day 1: standard, n-3 enriched or n-6 enriched diets. Depending on the diet, in endothelial cells LPS produced distinct regulation of pathways related to immune response, cell cycle, extracellular matrix, and angiogenesis. N-3 PUFA diet enabled higher immune reactivity in brain vasculature, while preventing imbalance of cell cycle regulation and extracellular matrix cascades that accompanied inflammatory response in standard diet. Cytokine analysis revealed a blunted LPS response in blood and brain of offspring from dams on n-3 enriched diet. Analysis of cerebral vasculature in offspring in vivo revealed no differences in vessel density. However, vessel complexity was decreased in response to LPS at 72 h in standard and n-6 diets. Thus, LPS modulates specific transcriptomic changes in brain vessels of offspring rather than major structural vessel characteristics during early life. N-3 PUFA-enriched maternal diet in part prevents an imbalance in homeostatic processes, alters inflammation and ultimately mitigates changes to the complexity of surface vessel networks that result from infection. Importantly, maternal diet may presage offspring neurovascular outcomes later in life. [ABSTRACT FROM AUTHOR]

The study of policy alone often means domestic policy, of interest to generalist sociologists interested in how political ideas are turned into domestic legislation, executive action, and/or court litigation. Foreign policy, as the financial, commercial, diplomatic and military relations of a state with foreign states, remains a niche subfield. But foreign relations should be conceived of as the broader set of entanglements between societies, encompassing transnational movements, expert networks, and fields. Then, sociological theories of foreign relations can interest generalist sociologists. In this review, we illustrate how this broad view of foreign relations applies to the study of the United States in the world today (USitWT) by first surveying how sociologists of the world society and world system have focused on transnational relations and the place of the United States in their dynamics, and how they have engaged with the question of power. We then demonstrate how field theorists' study of transnational fields can allow sociologists to reconceptualize the historical role of the USitWT by highlighting continuities between European colonial governmentalities and current US transnational practices. This field perspective can allow sociologists to understand the USitWT as transnational, postcolonial, or neo-colonial governmentality, depending on the sociological and historical depth and range of its relation with different parts of the world. [ABSTRACT FROM AUTHOR]

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host's response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high (n = 5) or medium (n = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls (n = 4), and with biased antibody-mediated (AbMR, n = 5) or cell-mediated (CMR, n = 5) adaptive immune responsiveness compared to uninfected controls (n = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection. [ABSTRACT FROM AUTHOR]

Background: The immersive and interactive nature of virtual reality (VR) renders it a potential pedagogical approach for nursing education. A bottleneck for exploiting VR advantages has been the complexity of creating new experiences; however, recent advances with VR hardware and software enable novice users to create compelling experiences. Method: A case study describes an undergraduate nursing student with minimal technical skills using off-the-shelf VR software to create a pain management VR experience. Results: Using off-the-shelf hardware and software platforms eliminates the need to work with computer code. The team created a virtual environment and the objects in it through easy manipulation with click-and-drag techniques and by toggling simple settings. Conclusion: The insights gained from this case suggest nurse educators can create simple yet powerful VR experiences themselves, which can greatly enhance existing tools for nursing education. [J Nurs Educ. 2024;63(4):261–264.] [ABSTRACT FROM AUTHOR]

Weight cycling is a major challenge in obesity management. Caloric restriction is known to promote this phenomenon, but the impact of macronutrient changes during dieting remains unclear. This study aimed to determine the role of macronutrient changes in weight maintenance without caloric restriction by alternating between two hypercaloric diets: a high-carbohydrate, high-fat Western diet (WD) and a low-carbohydrate, high-fat diet (LCHDF). Obesity was induced in 8-week-old C57BL/6 male mice by 10 weeks of WD feeding. Then, the mice were subjected to 12 weeks of LCHFD interspersed with WD (I-WD), 3 periods of 2-week LCHFD followed by 2 periods of 3-week WD, or 12 weeks of continuous WD (C-WD). C-WD and I-WD mice were compared to standard diet (SD) mice. In the I-WD group, each LCHFD period decreased weight gain, but mice regained weight after WD resumption. I-WD mice exhibited obesity, dyslipidemia, and glucose intolerance, similarly to the C-WD mice. I-WD mice also developed nonalcoholic steatohepatitis, associated with an increase in type-III collagen gene expression and a decrease in FGF21 protein levels, in comparison with SD. I-WD mice developed weight cycling despite maintaining a high caloric consumption, suggesting that changes in macronutrients during dieting are also a trigger of weight regain. [ABSTRACT FROM AUTHOR]

Background: Recruitment of cancer clinical trial (CCT) participants, especially participants representing the diversity of the US population, is necessary to create successful medications and a continual challenge. These challenges are amplified in Phase I cancer trials that focus on evaluating the safety of new treatments and are the gateway to treatment development. In preparation for recruitment to a Phase I recurrent head and neck cancer (HNC) trial, we assessed perceived barriers to participation or referral and suggestions for recruitment among people with HNC and community physicians (oncologist, otolaryngologist or surgeon). Methods: Between December 2020 and February 2022, we conducted a qualitative needs assessment via semistructured interviews with a race and ethnicity‐stratified sample of people with HNC (n = 30: 12 non‐Hispanic White, 9 non‐Hispanic African American, 8 Hispanic and 1 non‐Hispanic Pacific Islander) and community physicians (n = 16) within the University of Florida Health Cancer Center catchment area. Interviews were analyzed using a qualitative content analysis approach to describe perspectives and identify relevant themes. Results: People with HNC reported thematic barriers included: concerns about side effects, safety and efficacy; lack of knowledge and systemic and environmental obstacles. Physicians identified thematic barriers of limited physician knowledge; clinic and physician barriers and structural barriers. People with HNC and physicians recommended themes included: improved patient education, dissemination of trial information and interpersonal communication between community physicians and CCT staff. Conclusions: The themes identified by people with HNC and community physicians are consistent with research efforts and recommendations on how to increase the participation of people from minoritized populations in CCTs. This community needs assessment provides direction on the selection of strategies to increase CCT participation and referral. Patient or Public Contribution: This study focused on people with HNC and community physicians' lived experience and their interpretations of how they would consider a future Phase I clinical trial. In addition to our qualitative data reflecting community voices, a community member reviewed the draft interview guide before data collection and both people with HNC and physicians aided interpretation of the findings. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) is known to induce severe tissue damage, notably through mitochondrial dysfunction. Mitochondrial transplantation has emerged as a promising therapeutic strategy in cardiac IR; however, few studies have previously assessed its efficacy in the context of peripheral IR. Therefore, the objective of this study was to assess the effect of mitochondrial transplantation in a hindlimb model of IR injury. Thirty-six SWISS mice were divided into three groups: control (CTL, n ¼ 12), ischemiareperfusion (IR, n ¼ 12), and IR with mitochondrial transplantation (MT, n ¼ 12). Ischemia (2 h) was induced using the tourniquet model around the right hind limb in the IR and MT groups. In MT group, mitochondria isolated from the right rectus muscle, a nonischemic region, were injected shortly before reperfusion. Mitochondrial respiration, calcium retention capacity, and Western blotting analysis were performed 2 h after reperfusion. Compared with the CTL group, IR led to a decrease in the mitochondrial respiratory capacity, particularly for the basal state (30%; P ¼ 0.015), oxidative phosphorylation (36%; P ¼ 0.024), and calcium retention capacity (45%; P ¼ 0.007). Interestingly, mitochondrial transplantation partially restored these functions since no differences between MT and CTL groups were found. In addition, the administration of healthy mitochondria resulted in a positive regulation of redox balance and mitochondrial dynamics within the skeletal muscle. Although further investigations are needed to better characterize underlying mechanisms, mitochondrial transplantation represents a promising strategy in the setting of IRinduced muscular damage. NEW & NOTEWORTHY Ischemia-reperfusion injury leads to severe muscular damage. Even if prompt revascularization is the treatment of choice, muscular alterations can lead to severe sequalae as mitochondrial dysfunction. Accordingly, adjunctive strategies are needed to overcome the muscular damage. Mitochondrial transplantation has shown beneficial effects in cardiac ischemia-reperfusion, but its role in peripheral muscle is not well established. In this study, we found that mitochondrial transplantation partially restored muscular function when submitted to ischemia reperfusion. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematodes (GINs) can be a major constraint and global challenge to the sheep industry. These nematodes infect the small intestine and abomasum of grazing sheep, causing symptoms such as weight loss, diarrhea, hypoproteinemia, and anemia, which can lead to death. The use of anthelmintics to treat infected animals has led to GIN resistance, and excessive use of these drugs has resulted in residue traced in food and the environment. Resistance to GINs can be measured using multiple traits, including fecal egg count (FEC), Faffa Malan Chart scores, hematocrit, packed cell volume, eosinophilia, immunoglobulin (Ig), and dagginess scores. Genetic variation among animals exists, and understanding these differences can help identify genomic regions associated with resistance to GINs in sheep. Genes playing important roles in the immune system were identified in several studies in this review, such as the CFI and MUC15 genes. Results from several studies showed overlapping quantitative trait loci (QTLs) associated with multiple traits measuring resistance to GINs, mainly FEC. The discovery of genomic regions, positional candidate genes, and QTLs associated with resistance to GINs can help increase and accelerate genetic gains in sheep breeding programs and reveal the genetic basis and biological mechanisms underlying this trait. [ABSTRACT FROM AUTHOR]

This cohort study investigates the correlates of risk for disinhibited behaviors using electronic health record data of individuals in the Million Veteran Program. Key Points: Question: What are the correlates of risk for disinhibited behaviors in the US veterans population? Findings: In this cohort study including electronic health record data of 560 824 veterans, risk for disinhibited behaviors was associated with medical outcomes across all bodily systems, including substance use disorders, suicide and self-harm, liver disease, chronic airway obstruction, and viral hepatitis C. Many of these associations were significant across ancestry and after accounting for other comorbid problems. Meaning: Results suggest that risk for disinhibited behaviors was associated with many health outcomes of particular relevance within the veteran community. Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). Design, Setting, and Participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020. Exposures: PGSs for EXT, depression, schizophrenia, and suicide attempt. Main Outcomes and Measures: Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records. Results: Within the MVP (560 824 patients; mean [SD] age, 67.9 [14.3] years; 512 593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR], 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C. Conclusions and Relevance: Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population. [ABSTRACT FROM AUTHOR]

Background: Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell–cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice. Methods: Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry. Results: Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower. Conclusion: Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature–glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring. [ABSTRACT FROM AUTHOR]

Despite regulatory elements such as long non - coding RNAs representing most of the transcriptome, the functional understanding of long non - coding RNAs in relation to major health conditions including bovine mastitis is limited. This study examined the milk somatic cell transcriptome from udder quarters of 6 Holstein dairy cows to identify differentially expressed long non - coding RNAs using RNA - Sequencing. Ninety - four differentially expressed long non - coding RNAs are identified, 5 of which are previously annotated for gene name and length, 11 are annotated for gene name and 78 are novel, having no gene name or length previously annotated. Significant inflammatory response and regulation of immune response pathways (false discovery rate < 0.05) are associated with the differentially expressed long non - coding RNAs. QTL annotation analysis revealed 31 QTL previously annotated in the genomic regions of the 94 differentially expressed long non - coding RNAs, and the majority are associated with milk traits. This research provides a better understanding of long non - coding RNAs regulatory elements in milk somatic cells, which may enhance current breeding strategies for more adaptable or high mastitis resistant cattle. RNA-seq analysis of lncRNAs in Holstein dairy cows identifies lncRNA functional regulatory elements in milk somatic cells, which in turn may enhance cattle breeding strategies for mastitis resistance. [ABSTRACT FROM AUTHOR]

The interplay between climate-forced sea level change, erosional and depositional processes, and flexural isostasy in deep time on passive margin deltas remains poorly understood. We performed a series of conceptual simulations to investigate flexural isostatic responses to high-frequency fluctuations in water and sediment load associated with climatically driven sea level changes. We model a large drainage basin that discharges to a continental margin and produces a large deltaic depocenter, then prescribe synthetic and climatic-driven sea level curves of different frequencies to assess flexural response. Results show that flexural isostatic responses are bidirectional over 100–1000 kyr timescales and are in sync with the magnitude, frequency, and direction of sea level fluctuations and that isostatic adjustments play an important role in driving along-strike and cross-shelf river mouth migration and sediment accumulation. Our findings demonstrate that climate-forced sea level changes produce a feedback mechanism that results in self-sustaining creation of accommodation into which sediment is deposited and plays a major role in delta morphology and stratigraphic architecture. [ABSTRACT FROM AUTHOR]

Gut barrier dysfunction occurs commonly in patients with critical disorders, leading to the translocation of luminal toxic substances and bacteria to the bloodstream. Connexin 43 (Cx43) acts as a gap junction protein and is crucial for intercellular communication and the diffusion of nutrients. The levels of cellular Cx43 are tightly regulated by multiple factors, including polyamines, but the exact mechanism underlying the control of Cx43 expression remains largely unknown. The RNA-binding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of intestinal epithelial pathobiology. Here we show that HuR directly bound to Cx43 mRNA via its 30-untranslated region in intestinal epithelial cells (IECs) and this interaction enhanced Cx43 expression by stabilizing Cx43 mRNA. Depletion of cellular polyamines inhibited the [HuR/Cx43 mRNA] complex and decreased the level of Cx43 protein by destabilizing its mRNA, but these changes were prevented by ectopic overexpression of HuR. Polyamine depletion caused intestinal epithelial barrier dysfunction, which was reversed by ectopic Cx43 overexpression. Moreover, overexpression of checkpoint kinase 2 in polyamine-deficient cells increased the [HuR/Cx43 mRNA] complex, elevated Cx43 levels, and promoted barrier function. These findings indicate that Cx43 mRNA is a novel target of HuR in IECs and that polyamines regulate Cx43 mRNA stability via HuR, thus playing a critical role in the maintenance of intestinal epithelial barrier function. NEW & NOTEWORTHY The current study shows that polyamines stabilize the Cx43 mRNA via HuR, thus enhancing the function of the Cx43-mediated gap junction. These findings suggest that induced Cx43 by HuR plays a critical role in the process by which polyamines regulate intestinal epithelial barrier. [ABSTRACT FROM AUTHOR]

Phenological indicators (PI) are used to study changes to animal and plant behavior in response to seasonal cycles, and they can be useful to quantify the potential impacts of climate change on ecosystems. Here, multiple global climate models and emission scenarios are used to drive dynamically downscaled simulations using the WRF Model over the contiguous United States (CONUS). The wintertime dormancy of plants [chilling units (CU)], timing of spring onset [extended spring indices (SI)], and frequency of proceeding false springs are calculated from regional climate simulations covering historical (1995-2005) and future periods (2025-2100). Southern parts of the CONUS show projected CU decreases (inhibiting some plants from flowering or fruiting), while the northern CONUS experiences an increase (possibly causing plants to break dormancy too early, becoming vulnerable to disease or freezing). Spring advancement (earlier SI dates) is projected, with decadal trends ranging from approximately 1-4 days per decade over the CONUS, comparable to or exceeding those found in observational studies. Projected changes in risk of false spring (hard freezes following spring onset) vary across members of the ensemble and regions of the CONUS, but generally western parts of the CONUS are projected to experience increased risk of false springs. These projected changes to PI connote significant effects on cycles of plants, animals, and ecosystems, highlighting the importance of examining temperature changes during transitional seasons. SIGNIFICANCE STATEMENT: This study examines how phenological indicators, which track the life cycles of plants and animals, could change from 2025 to 2100 as simulated in a regional climate model over the contiguous United States. Chilling units quantify the presence of cooler weather that can benefit plants prior to their growing season. They are projected to decrease in the southern United States, possibly inhibiting agricultural production. Spring onset is projected to occur earlier in the year, advancing by 1-4 days on average over each future decade. Risk of false springs (damaging hard freezes after spring onset) increases in the western United States. Our findings highlight the need to understand effects of climate change during transitional seasons, which can impact agriculture and ecosystems. [ABSTRACT FROM AUTHOR]

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, although down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci; the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses were found robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who generate and share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers' use of the summary statistics. [ABSTRACT FROM AUTHOR]

A clinical challenge remains in the treatment of hypoxic–ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia–ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia–ischemia. At different time points after hypoxia–ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia–ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia–ischemia in mice suggesting as a possible novel treatment for neonatal brain injury. Summary Statement: Neonatal hypoxia–ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus. Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia–ischemia. Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release. NMN improves early developmental behavior, as well as motor and memory function. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3–4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. Methods: We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. Results: PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC), an acetylated derivative of the amino acid L-cysteine, has been widely used as a mucolytic agent and antidote for acetaminophen overdose since the 1960s and the 1980s, respectively. NAC possesses antioxidant, cytoprotective, anti-inflammatory, antimicrobial, and mucolytic properties, making it a promising therapeutic agent for a wide range of diseases in both humans and domesticated animals. Oxidative stress and inflammation play a major role in the onset and progression of all these diseases. NAC's primary role is to replenish glutathione (GSH) stores, the master antioxidant in all tissues; however, it can also reduce levels of pro-inflammatory tumor necrosis factor-alpha (TNF-∝) and interleukins (IL-6 and IL-1β), inhibit the formation of microbial biofilms and destroy biofilms, and break down disulfide bonds between mucin molecules. Many experimental studies have been conducted on the use of NAC to address a wide range of pathological conditions; however, its effectiveness in clinical trials remains limited and studies often have conflicting results. The purpose of this review is to provide a concise overview of promising NAC usages for the treatment of different human and domestic animal disorders. [ABSTRACT FROM AUTHOR]

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) are phenotypically and genetically correlated with each other and with other psychological traits characterized by behavioural under‐control, termed externalizing phenotypes. In this study, we used genomic structural equation modelling to explore the shared genetic architecture among six externalizing phenotypes and four SUDs used in two previous multivariate genome‐wide association studies of an externalizing and an addiction risk factor, respectively. We first evaluated five confirmatory factor analytic models, including a common factor model, alternative parameterizations of two‐factor structures and a bifactor model. We next explored the genetic correlations between factors identified in these models and other relevant psychological traits. Finally, we quantified the degree of polygenic overlap between externalizing and addiction risk using MiXeR. We found that the common and two‐factor structures provided the best fit to the data, evidenced by high factor loadings, good factor reliability and no evidence of concerning model characteristics. The two‐factor models yielded high genetic correlations between factors (rgs ≥ 0.87), and between the effect sizes of genetic correlations with external traits (rg ≥ 0.95). Nevertheless, 21 of the 84 correlations with external criteria showed small, significant differences between externalizing and addiction risk factors. MiXer results showed that approximately 81% of influential externalizing variants were shared with addiction risk, whereas addiction risk shared 56% of its influential variants with externalizing. These results suggest that externalizing and addiction genetic risk are largely shared, though both constructs also retain meaningful unshared genetic variance. These results can inform future efforts to identify specific genetic influences on externalizing and SUDs. [ABSTRACT FROM AUTHOR]

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematodes (GINs) are a major constraint to the sheep industry. Infected animals can develop clinical signs, like anemia, hypoproteinemia, diarrhea, and in extreme cases death. The misuse of anthelmintics to treat infected animals has led to the development of GIN resistance making necessary the integration of different approaches to reduce the impact of GINs on the sheep industry. The application of transcriptomics using RNA-Sequencing technology to better understand the underlying genetic mechanisms of resistance to GIN can help accelerate the genetic gain. This study aimed to identify insertion and deletions (INDELs) responsible for alternative splicing in Rideau x Dorset crossbred sheep with different immune profiles under natural exposure to gastrointestinal nematodes using RNA-Sequencing. High (H) and medium (M) acute stress responders with the highest and lowest worm burden, after natural exposure to GIN, were selected for liver RNA extraction (H; n = 5 and M; n = 6). In addition, GIN-unexposed lambs (U; n = 4) were used as immunological controls. Quality control analyses were performed on fastq files using the CLC Bio Genomics workbench software including the guanine-cytosine (GC) content, ambiguous base content, Phred score, base coverage, nucleotide contributions, and over-represented sequence parameters. Pair-end sequence reads were aligned to the annotated Oar_rambouillet_v.2.0 ovine reference genome. After that, variant discovery analysis and functional consequence analysis were performed using CLC Bio Genomics workbench software to identify INDELs leading to amino acid changes and splice site events (SSEs). Genes associated with the list of INDELs leading to SSE were recovered from Ensembl BioMart. Unique INDELs with SSEs for H, M, and U groups (162, 244, and 161, respectively) and shared (372) among groups were identified. Among them, 4 INDELS with SSE uniquely identified in the M group were located within the NLRC5, SIGLEC1, CFD, and STAT6 genes related to the immune system. Significant enriched metabolic pathways (FDR< 0.05) were identified using the list of genes with INDELs that led to SSEs unique for each group and shared among groups using Reactome. Metabolic pathways related to the immune system response such as cross-presentation of soluble exogenous antigens (endosomes) and NIK noncanonical NF-kB signaling pathways were identified in the M group. These results can help to better understand the mechanisms responsible for the immune response of sheep to GIN. [ABSTRACT FROM AUTHOR]

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments. [ABSTRACT FROM AUTHOR]

In this study, we assess the scattering of light and auto-fluorescence from single bacterial cells to address the challenge of fast (<2  h), label-free phenotypic antimicrobial susceptibility testing (AST). Label-free flow cytometry is used for monitoring both the respiration-related auto-fluorescence in two different fluorescence channels corresponding to FAD and NADH, and the morphological and structural information contained in the light scattered by individual bacteria during incubation with or without antibiotic. Large multi-parameter data are analyzed using dimensionality reduction methods, based either on a combination of 2D binning and Principal Component Analysis, or with a one-class Support Vector Machine approach, with the objective to predict the Susceptible or Resistant phenotype of the strain. For the first time, both Escherichia coli (Gramnegative) and Staphylococcus epidermidis (Gram-positive) isolates were tested with a label-free approach, and, in the presence of two groups of bactericidal antibiotic molecules, aminoglycosides and beta-lactams. Our results support the feasibility of label-free AST in less than 2  h and suggest that single cell autofluorescence adds value to the Susceptible/Resistant phenotyping over singlecell scattering alone, in particular for the mecA+ Staphylococcus (i.e., resistant) strains treated with oxacillin. [ABSTRACT FROM AUTHOR]

Background: A steady decline in the number of cases of malaria was observed in the 2000s in French Guiana. This enabled regional health policies to shift their public health goal from control to elimination. To include inhabitants in this strategy, the main objective of this study was to describe knowledge about malaria, and related attitudes and practices in persons living in the French Guiana border. Methods: We conducted a survey in people over 15 years old living in the twelve neighbourhoods of Saint-Georges de l'Oyapock with the highest malaria incidence. It comprised a 147-item questionnaire which collected data on socio-demographic characteristics and included a Knowledge Attitude and Practices survey on malaria. Knowledge-related data were studied using exploratory statistical methods to derive summary variables. A binary variable assessing level of knowledge was proposed and then assessed using exploratory approaches. Results: The mean age of the 844 participants was 37.2 years [15.8], the male/female sex ratio was 0.8. In terms of nationality, 485 (57.5%) participants were Brazilian and 352 (41.7%) French. One third (305, 36.1%) spoke Brazilian Portuguese as their native language, 295 (34.9%) the Amerindian language Palikur, 36 (4.3%) French. The symptoms of malaria and prevention means were poorly known by 213 (25.2%) and 378 (44.8%) respondents, respectively. A quarter (206, 24.4%) did not know that malaria can be fatal. Overall, 251 people (29.7%) had an overall poor level of knowledge about malaria. Being under 25 years old, living in a native Amerindian neighbourhood, having an Amerindian mother tongue language, having risk behaviours related to gold mining were significantly associated with a poor level of knowledge. Conclusions: This study is the first to describe the poor level of knowledge about malaria in populations living in the malaria endemic border area along the Oyapock river in French Guiana. Results will allow to reinforce, to diversify and to culturally adapt prevention messages and health promotion to increase their effectiveness with a view to quickly reaching the goal of malaria elimination through empowerment. [ABSTRACT FROM AUTHOR]

Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform‐specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN‐KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs‐iOPN‐KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN‐KO mice compared to control mice. Accordingly, adult OPN‐KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin‐related proteins. In contrast, neonatal oligodendrocytes from OLs‐iOPN‐KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs‐iOPN‐KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform‐specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases. [ABSTRACT FROM AUTHOR]

Context The Food and Agriculture Organization of the United Nations and the World Health Organization are updating their dietary zinc recommendations for children aged 0 to 3 years. Objective The aim of this review was to retrieve and synthesize evidence regarding zinc needs for growth as well as zinc losses, absorption, and bioavailability from the diet. Data Sources MEDLINE, Embase, and Cochrane Library databases were searched electronically from inception to August 2020. Studies assessing the above factors in healthy children aged 0 to 9 years were included, with no limits on study design or language. Data Extraction Ninety-four studies reporting on zinc content in tissue (n = 27); zinc absorption (n = 47); factors affecting zinc bioavailability (n = 30); and endogenous zinc losses via urine, feces, or integument (n = 40) met the inclusion criteria. Four reviewers extracted data and two reviewers checked for accuracy. Data Analyses Studies were synthesized narratively, and meta-analyses of zinc losses and gains as well the subgroups of age, type of feeding, country's income, and molar ratio of phytate to zinc were conducted. Meta-analysis revealed an overall mean (95%CI) urinary and endogenous fecal zinc excretion of 17.48 µg/kg/d (11.80–23.15; I2  = 94%) and 0.07 mg/kg/d (0.06–0.08; I2  = 82%), respectively, with a mean fractional zinc absorption of 26.75% (23.69–29.81; I2  = 99%). Subgrouping by age revealed differences in mean values associated with the transition from milk-based diets to solid food during the first 3 years of life. Conclusion This review synthesizes data that may be used to formulate zinc requirements in young children. Results should be interpreted with caution because of considerable heterogeneity in the evidence. Systematic Review Registration PROSPERO registration number CRD42020215236. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can genes be identified whose expression is associated with cross-disorder psychiatric risk along with existing drugs that target these genes? Findings: In this genetic association study, transcriptome-wide structural equation modeling was used to identify 466 genes associated with psychiatric genomic factors that index shared risk across subsets of disorders. Results revealed 35 drug-gene pairs that may target shared risk pathways across bipolar disorder and schizophrenia and 5 drug-gene with potential transdiagnostic effect. Meaning: Identified genes yielded insight into the biological pathways shared across genetically overlapping disorders and as such may reflect efficacious drug targets for comorbid or mixed clinical presentations. This genetic association study identifies gene expression patterns underlying genetic convergence and divergence across psychiatric disorders along with existing pharmacological interventions that target these genes using transcriptome-wide structural equation modeling (T-SEM). Importance: Psychiatric disorders display high levels of comorbidity and genetic overlap, necessitating multivariate approaches for parsing convergent and divergent psychiatric risk pathways. Identifying gene expression patterns underlying cross-disorder risk also stands to propel drug discovery and repurposing in the face of rising levels of polypharmacy. Objective: To identify gene expression patterns underlying genetic convergence and divergence across psychiatric disorders along with existing pharmacological interventions that target these genes. Design, Setting, and Participants: This genomic study applied a multivariate transcriptomic method, transcriptome-wide structural equation modeling (T-SEM), to investigate gene expression patterns associated with 5 genomic factors indexing shared risk across 13 major psychiatric disorders. Follow-up tests, including overlap with gene sets for other outcomes and phenome-wide association studies, were conducted to better characterize T-SEM results. The Broad Institute Connectivity Map Drug Repurposing Database and Drug-Gene Interaction Database public databases of drug-gene pairs were used to identify drugs that could be repurposed to target genes found to be associated with cross-disorder risk. Data were collected from database inception up to February 20, 2023. Main Outcomes and Measures: Gene expression patterns associated with genomic factors or disorder-specific risk and existing drugs that target these genes. Results: In total, T-SEM identified 466 genes whose expression was significantly associated (z ≥ 5.02) with genomic factors and 36 genes with disorder-specific effects. Most associated genes were found for a thought disorders factor, defined by bipolar disorder and schizophrenia. Several existing pharmacological interventions were identified that could be repurposed to target genes whose expression was associated with the thought disorders factor or a transdiagnostic p factor defined by all 13 disorders. Conclusions and Relevance: The findings from this study shed light on patterns of gene expression associated with genetic overlap and uniqueness across psychiatric disorders. Future versions of the multivariate drug repurposing framework outlined here have the potential to identify novel pharmacological interventions for increasingly common, comorbid psychiatric presentations. [ABSTRACT FROM AUTHOR]

The hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes Tnfrsf1a and Il6ra, and Hgf gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of Col1a1, Col1a2, Col5a1, and Col6a2 compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process. [ABSTRACT FROM AUTHOR]